Neuroinflammation in the NTS is associated with changes in cardiovascular reflexes during systemic inflammation

Mateus R Amorim,Clarissa M D Mota,Evelin C Cárnio,Júnia L De Deus,Rafael A Cazuza,Luiz G S Branco,Marcelo E Batalhão,Luiz E V Da Silva,Gabriela S Borges

doi:10.1186/s12974-019-1512-6

Abstract

BackgroundLipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions. Considering that during SI these important cardiovascular and inflammatory changes take place, we measured the sensitivity of the cardiovascular reflexes baroreflex, chemoreflex, and Bezold-Jarisch that are key regulators of hemodynamic function. We also evaluated neuroinflammation in the nucleus tractus solitarius (NTS), the first synaptic station that integrates peripheral signals arising from the cardiovascular and inflammatory status.MethodsWe combined cardiovascular recordings, immunofluorescence, and assays of inflammatory markers in male Wistar rats that receive iv administration of LPS (1.5 or 2.5 mg kg−1) to investigate putative interactions of the neuroinflammation in the NTS and in the anteroventral preoptic region of the hypothalamus (AVPO) with the short-term regulation of blood pressure and heart rate.ResultsLPS induced hypotension, tachycardia, autonomic disbalance, hypothermia followed by fever, and reduction in spontaneous baroreflex gain. On the other hand, during SI, the bradycardic component of Bezold-Jarisch and chemoreflex activation was increased. These changes were associated with a higher number of activated microglia and interleukin (IL)-1β levels in the NTS.ConclusionsThe present data are consistent with the notion that during SI and neuroinflammation in the NTS, rats have a reduced baroreflex gain, combined with an enhancement of the bradycardic component of Bezold-Jarisch and chemoreflex despite the important cardiovascular impairments (hypotension and tachycardia). These changes in the cardiac component of Bezold-Jarisch and chemoreflex may be beneficial during SI and indicate that the improvement of theses reflexes responsiveness though specific nerve stimulations may be useful in the management of sepsis.

Highlights

Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions
To verify whether the drop in Mean arterial pressure (MAP) and tachycardia persist 24 h after LPS was given, we evaluated rats on the day after the treatment, and observed that MAP values reduced at 3 h, but returned to nadir levels in (24 h) group (P > 0.05, Fig. 2c)
To provide mechanistic insights involved in autonomic control of heart and resistance vessels, spectral analysis of pulse interval (PI) and systolic arterial pressure (SAP) was done and data are showing that Low frequency (LF) component of PI was not affected by SI (P > 0.05, Fig. 2e)

Summary

Introduction

Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions. We evaluated neuroinflammation in the nucleus tractus solitarius (NTS), the first synaptic station that integrates peripheral signals arising from the cardiovascular and inflammatory status. Acute activation of innate immunity during infection or injury is an evolutionary trend protecting organisms against threats [1]. Exacerbated release of proinflammatory mediators, observed during systemic inflammation (SI), causes severe tissue hypoperfusion contributing to multiple organ dysfunction in septic patients [2,3,4]. It is essential to investigate the acute and long-term cardiovascular complications after SI. Used as the most accepted experimental model of SI, bacterial compounds, such as the lipopolysaccharide(LPS), have emerged as the major source of the cellular

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